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Results for “Comparative transcriptomics”

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PubMed2026

Proteomic analysis of pancreatic endocrine cells by mechanistic single-cell isolation identifies membrane pathways.

To better understand diabetes and normoglycemia, pancreatic islet biology requires a precise molecular understanding of islet cell types at both the transcriptomic and proteomic levels. While transcriptomic analyses are well established, comprehensive proteomic characterization has been lacking, limiting our knowledge of islet molecular complexity. Here we introduce a nonenzymatic, mechanistic single-cell isolation technology using laser microdissection (LMD7), facilitating proteomic and transcriptomic analysis of physically isolated α-, β- and δ-cells from fresh-frozen, unfixed pancreatic tissue. This mechanistic approach avoids enzymatic digestion and chemical fixation, preserving the cells' native molecular state before processing. Given the limited existing proteomic data, we supplemented our findings with transcriptomic analysis generated using the same method and compared our results with data from enzymatically isolated cells, obtained by fluorescence-activated cell sorting and compiled by others. Our analysis revealed that enzymatic digestion alters gene expression patterns, particularly those of membrane-associated proteins, underscoring the impact of isolation techniques on biological outcomes. We identified cell-type-specific proteins typically underrepresented in pancreatic single-cell transcriptomic datasets. β-cells exhibited enrichment in vesicle trafficking proteins, α-cells displayed distinct calcium-dependent action potential machinery and δ-cells showed elevated expression of focal adhesion-related proteins. In addition, we report an inverse molecular relationship between β- and δ-cells, potentially driven by transcriptional regulators such as Mlxipl. By establishing robust molecular profiles directly from intact pancreatic tissue, this work provides a reference point for future pathological comparisons, offering a framework to investigate how diabetes and other endocrine disorders reshape islet cell biology.

Journal Article↗

PubMed2026

Deciphering novel targets in salivary gland pleomorphic adenoma by integrating plasma proteomics and parotid transcriptomics analyses.

BACKGROUND/PURPOSE: Pleomorphic adenoma (PA) is the most common salivary gland benign tumor, with its molecular drivers elusive due to a lack of experimental models. This study aimed to decipher novel targets in PA by systematically integrating plasma protein quantitative trait loci (pQTL)-based Mendelian randomization (MR) with multi-omics profiling of parotid gland tissues. MATERIALS AND METHODS: We performed two-sample MR using 5450 plasma pQTLs and genome-wide association study summary for benign or broader salivary gland diseases from FinnGen consortium. Bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) comparing PA to normal tissue were used for transcriptomic validation. Immunohistochemistry (IHC) was applied for protein-level validation in human PA, adenoid cystic carcinoma (ACC), and murine inflammatory lesions. RESULTS: MR identified 12 plasma proteins associated with benign salivary gland tumor risk. Transmembrane serine protease 6 (TMPRSS6) was the only protein significantly risk-increasing for both benign and broader salivary gland diseases. Strikingly, mitogen-activated protein kinase kinase 4 (MAP2K4) showed opposite MR effects between benign and all-lesion outcomes. Bulk RNA-seq showed limited concordance with MR findings, while scRNA-seq revealed a unique plastic epithelium and partially validated candidates at cellular resolution. Critically, IHC confirmed MAP2K4 protein overexpression specifically in human PA, but not in ACC or inflammatory lesions, while TMPRSS6 was downregulated in established pathologies despite its genetic risk association. CONCLUSION: By integrating plasma proteome-based causal inference with parotid tissue multi-omics, this study unveils MAP2K4 as a potential PA-specific driver. This integrative framework provides novel, context-specific targets for further functional investigation in salivary gland tumorigenesis.

Gene expression profiling↗

PubMed2025

Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats.

To date, no clinical trial has investigated the potential of CD34+ cells to treat diabetic nephropathy. This study examined the efficacy of human CD34+ cells against diabetic nephropathy in rats. Rats were administered streptozotocin (STZ) intraperitoneally and divided into three groups: normal control, STZ control, and STZ plus cell therapy. The STZ-plus-cell-therapy group was administered human umbilical cord blood-derived CD34+ cells weekly for three weeks. At eight weeks, the rats' renal function, pathology, and transcriptome profiles were assessed. Although blood glucose levels did not differ between the STZ-administered groups, urinary albumin excretion was significantly lower at 6 weeks in the STZ-plus-cell-therapy group than in the STZ control group (p < 0.001). Serum creatinine levels tended to be higher in the STZ control group and lower in the STZ-plus-cell-therapy group. Cell therapy significantly improved mesangial expansion, interstitial fibrosis, peritubular capillary rarefaction, and glomerular macrophage infiltration compared with the STZ control (p < 0.0001). Kidney transcriptomics revealed significant upregulation of genes related to M2 macrophage markers, cell homing, and angiogenesis in the STZ-plus-cell-therapy group. In rats with STZ-induced diabetic nephropathy, human CD34+ cells ameliorated renal injury through their anti-inflammatory and pro-angiogenic effects.

Animals↗

PubMed2026

Transcriptomic Insights into Acupuncture Mechanisms in Protecting Ovarian Function in Mice with Premature Ovarian Insufficiency.

OBJECTIVE: To explore the molecular mechanisms underlying the protective effect of acupuncture on ovarian function in mice with cyclophosphamide-induced premature ovarian insufficiency (POI) via transcriptomic analysis. METHODS: Twenty female C57BL/6 mice were divided into 4 groups: control, model, acupuncture, and non-meridian/non-acupoint (NOMA). POI was induced in the model, acupuncture, and non-meridian/non-acupoint groups via cyclophosphamide injection. The acupuncture group received acupuncture at Guanyuan (CV 4), bilateral Guilai (ST 29), and Sanyinjiao (SP 6) for 3 weeks. After the intervention, ovarian tissue weight and ovarian coefficient were calculated, serum levels of key reproductive hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were detected, and ovarian histopathological changes were observed to evaluate ovarian function. Transcriptome sequencing was performed to identify differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore key functional terms and signaling pathways. Western blot was finally applied to validate the expression of core proteins related to mitochondrial function, endoplasmic reticulum stress and inflammatory pathways. RESULTS: The model group showed reduced ovarian weight and elevated FSH levels. The acupuncture group exhibited significantly higher ovarian weight and coefficient, lower FSH levels, and increased E2 and AMH levels compared to the model group (all P<0.01). Transcriptomic analysis revealed 4,021 DEGs between groups. GO and KEGG analyses revealed that these DEGs were mainly involved in oocyte development, steroid hormone synthesis, and pathways related to mitochondrial function, endoplasmic reticulum stress, and inflammatory signaling. Western blot analysis showed that acupuncture partially restored mitochondrial function markers cytochrome c oxidase subunit IV and NADH dehydrogenase 1 beta subcomplex subunit 8 and reduced endoplasmic reticulum stress markers (glucose-regulated protein 78 and Calnexin, P<0.01). It also downregulated pro-inflammatory proteins (IL-17R, IL-17A, NF-κB p65, p-NF-κB p65, ERK1/2, and p-ERK1/2) and upregulated proteins related to metabolic homeostasis (peroxisome proliferator-activated receptor γ, receptor-interacting protein 140, nicotinamide phosphoribosyltransferase, and sirtuin 1, P<0.01). CONCLUSION: Acupuncture effectively alleviates cyclophosphamide-induced POI in mice, improves ovarian function and follicular quality by regulating cellular functions and inflammatory pathways, suggesting a novel therapeutic approach for POI.

acupuncture↗

PubMed2001

Heart transplantation changes the expression of distinct gene families.

We took advantage of the combination of a rat heart transplantation model with a modified differential display RT-PCR method to identify transcriptome changes in the right atria from transplanted compared with native hearts. Based on sequence homology search, the 37 cDNAs differentially displayed both 2 and 7 days posttransplantation were categorized into 7 unknown transcripts, 16 expressed sequence tags (ESTs), and 14 partially or completely characterized genes. The last group cDNAs, validated by relative RT-PCR, belonged to diverse gene families involved in specific metabolisms, protein synthesis, cell signaling, and transcription. Furthermore, we identified differential transcripts corresponding to denervation and fetal gene reexpression. We found coordinate downregulation of genes involved in energy metabolism and protein synthesis regulation, similar to that reported for senescent skeletal muscle. From these transcriptome changes, we propose that heart transplants and senescent muscles share common molecular mechanisms.

Animals↗

PubMed2025

EucaMOD: a comprehensive multi-omics database for functional genomics research and molecular breeding of fast-growing eucalyptus trees.

Eucalyptus, one of the most widely planted plantation tree species globally, is primarily found in tropical and subtropical regions and contributes significantly to economic and social benefits. With advances in sequencing technologies, there is an increasing demand for the systematic analysis of multi-omics data among Eucalyptus species to enhance genetic breeding efforts. Although several early genomic databases have been established for eucalyptus, they have not been updated in a timely manner and lack recent multi-omics data, rendering them insufficient for current research needs. To address this gap, we developed the eucalyptus multi-omics database (EucaMOD, http://eucalyptusggd.net/eucamod), a comprehensive resource for cross-omics studies. In this study, we functionally annotated 45 eucalyptus genomes and structurally annotated 15, conducting comparative genomics and pan-proteomics analyses across all genomes. Additionally, we analyzed eucalyptus transcriptome, epigenome, and variome data through standardized workflows, enabling the in-depth mining and reanalysis of multi-omics datasets. EucaMOD is the most comprehensive multi-omics database for eucalyptus to date and includes data from 45 genomes (39 species), 870 mRNA-seq samples, 17 miRNA-seq samples, 52 epigenomic datasets (histone modifications and transcription factor binding), and genetic variation data from 1219 samples. To support functional genomics and molecular breeding research, the database is organized into the following 11 modules: Home, Species, Genomics, Comparative genomics, Pan-proteomics, Transcriptomics, Epigenetics, Variomics, Tools, Download, and Help. EucaMOD also offers online analysis tools for data mining, providing free public services to aid eucalyptus gene function and genetic engineering studies.

Eucalyptus↗

PubMed2025

Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection.

At this stage in the COVID-19 pandemic, most infections are "breakthrough" infections that occur in individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity in breakthrough infections. We performed single-cell transcriptomic, proteomic, and functional profiling of primary and breakthrough infections to compare immune responses from unvaccinated and vaccinated individuals during the SARS-CoV-2 Delta wave. Breakthrough infections were characterized by a less activated transcriptomic profile in monocytes and natural killer cells, with induction of pathways limiting monocyte migratory potential and natural killer cell proliferation. Furthermore, we observed a female-specific increase in transcriptomic and proteomic activation of multiple innate immune cell subsets during breakthrough infections. These insights suggest that prior SARS-CoV-2 vaccination prevents overactivation of innate immune responses during breakthrough infections with discernible sex-specific patterns and underscore the potential of harnessing vaccines in mitigating pathologic immune responses resulting from overactivation.

Immunity, Innate↗

PubMed2026

A 3D in vitro co-culture model to investigate tumor-endothelial interactions in Neurofibromatosis type 2-associated meningiomas.

BACKGROUND: Neurofibromatosis type 2 (NF2)-associated meningiomas and schwannomas are vascular tumors, and while vascular endothelial growth factor (VEGF) inhibition with bevacizumab has benefited some NF2-related schwannomas, most NF2-associated meningiomas remain nonresponsive. METHODS: Leveraging our transcriptomic data, we performed Gene Ontology (GO) analysis comparing NF2-deficient meningioma cells with NF2-expressing arachnoid cells (ACs). We then established a 3D in vitro angiogenesis model by co-culturing NF2-null meningioma cells with human umbilical vein endothelial cells (HUVECs). Endothelial sprouting was assessed by CD31/PECAM immunostaining. Effects of third-generation mechanistic target of rapamycin complex 1 (mTORC1)-selective inhibitor RMC-6272 as well as APLN knock-out using CRISPR-Cas9 gene editing were also examined. RESULTS: GO analysis identified vascular development among the top significantly upregulated pathways in NF2-deficient cells. In 3D co-culture, ECs formed radially sprouting tube-like networks from the spheroid surface, and our data supports an angiogenesis phenotype driven by meningioma cells. Given these results along with hyperactivation of mTORC1 upon NF2-deficiency, we examined whether RMC-6272 disrupts meningioma-driven angiogenesis. RMC-6272 potently suppressed EC sprouting. Cross-referencing baseline transcriptomic data, we identified Apelin (APLN), the ligand for APLN receptor (APLNR), as a basally upregulated angiogenic factor in NF2-deficient meningiomas. Quantitative RT-PCR (qRT-PCR) confirmed increased APLN expression in NF2-null immortalized and patient-derived meningioma lines, with reduced expression upon mTORC1 inhibition. Apelin-13 stimulation enhanced sprouting, whereas APLN deletion reduced endothelial sprouting. CONCLUSIONS: Here we establish a 3D-tumoroid model and implicate tumor-derived Apelin as an important contributor to NF2-associated meningioma angiogenesis. Our data also suggest that APLN expression is regulated, at least in part, by mTORC1. Together, these results provide a preclinical platform for investigating angiogenic vulnerabilities beyond VEGF in NF2-deficient meningiomas.

3D tumoroid model↗

PubMed2026

De Novo Genome Sequence Assembly of the Algal Endosymbiont Micractinium conductrix Derived From Its Host Paramecium bursaria 186b.

Endosymbiosis is a major driver of evolutionary innovation and underpins the function of diverse ecosystems. The origins and evolution of endosymbiosis are challenging to study experimentally due to the short-lived culturability of many microbial strains derived from endosymbiotic interactions. The facultative endosymbiosis between the ciliate, Paramecium bursaria, and the green alga, Micractinium conductrix (Chlorellaceae, Trebouxiophyceae), is ecologically widespread and has emerged as a powerful lab-tractable model system. This endosymbiosis is founded upon a reciprocal nutrient exchange, but each of the species can be cultured independently enabling quantification of symbiotic fitness effects, new partnerships to be generated in the lab, and co-associations to be subject to experimental evolution. To date, evolve-and-resequence approaches have been limited due to a lack of high-quality genome assemblies enabling gene variants to be identified. Here, we report a near telomere-to-telomere genome assembly for M. conductrix 186b, using a range of sequencing technologies. Comparative analysis shows that this is one of the most complete Chlorellaceae algal genome assemblies available to date. To aid accurate gene calling and annotation, we conducted both RNAseq and Iso-Seq transcriptome sequencing experiments. Collectively, these 'omics datasets will facilitate: (i) comparative genomics studies of endosymbiont evolution, (ii) evolve-and-resequence experiments, (iii) genome-scale metabolic modeling studies, and (iv) identification of targets for genetic modification experiments and biotechnological applications.

Symbiosis↗

PubMed2002

Toward a universal standard: comparing two methods for standardizing spotted microarray data.

DNA microarray technology has allowed the transcriptome to be studied to a depth that was inconceivable only 10 years ago. Until recently these studies were isolated because, without a universal standard, the results from experiment to experiment and laboratory to laboratory were not directly comparable. For human microarrays, this problem has been addressed by numerous methods, but only two are truly universal. The first method uses genomic DNA as a standard for comparison since it is, by definition, complete and universally available. The second method employs a highly representative total RNA pool such as the one currently available from Stratagene. To determine the advantages and disadvantages of both methods, they were directly compared by hybridization to the University of Texas Southwestern Medical Center's 4000- or 10800-member human cDNA array, using typical microarray techniques. The labeled analytes were 2 microg normal human genomic DNA labeled by nick translation or 20 microg total RNA pool labeled by reverse transcription. The resulting data were then background-subtracted, analyzed, and the number of spots above a background threshold was compared in each sample. Using the McNemar test and a Yate's correction with one degree of freedom, the samples were statistically identical with chi2 = 3.72.

DNA↗

PubMed2026

scGPA: an LLM-assisted workflow for directional virtual gene perturbation analysis from single-cell transcriptomes.

BACKGROUND: Existing virtual perturbation methods can often infer directional changes by comparing predicted post-perturbation expression profiles with control cells. However, workflows that directly return direction-specific downstream candidate genes together with confidence scores, evidence support and interpretable summaries remain limited. We developed scGPA, an LLM-assisted workflow system for directional single-cell virtual gene perturbation analysis. METHODS: scGPA starts from raw single-cell RNA sequencing data and performs quality control, normalization, dimensionality reduction, clustering and cell-group selection. It then constructs cell-group-specific wild-type regulatory networks using repeated subsampling, principal component regression (PCR)/Ridge-based network inference and CP tensor denoising. Based on these networks, scGPA simulates dose-aware virtual knockdown of the target gene and applies signed perturbation propagation to estimate the magnitude and direction of downstream transcriptional responses. LLM assistance is used for marker-based cell-type annotation, evidence-guided candidate prioritization and user-facing biological summarization. RESULTS: We benchmarked scGPA across five public Perturb-seq datasets and compared its performance with GEARS, scGPT and a random baseline. The overall correct prediction rate of scGPA was 23.0%, exceeding those of GEARS (20.7%), scGPT (15.1%) and the random baseline (13.6%). These results indicate that scGPA achieved a higher correct prediction rate than the two comparator models and the random baseline. We subsequently evaluated scGPA using a public osteosarcoma single-cell dataset and performed qRT-PCR validation in 143B osteosarcoma cells. Among genes with significant experimental changes, scGPA achieved a directional concordance of 76.9%. When all tested downstream genes were counted, 37.0% were directionally correct, 51.9% showed no significant change and 11.1% changed in the opposite direction. CONCLUSIONS: scGPA provides a practical workflow system for predicting and prioritizing direction-specific downstream transcriptional responses after target-gene perturbation. By integrating single-cell regulatory network inference, signed virtual perturbation and LLM-assisted interpretation, scGPA supports target-gene function inference and downstream mechanistic investigation from single-cell transcriptomic data.

Single-Cell Gene Expression Analysis↗

PubMed2026

Multi-omics reveal molecular changes during suspension adaptation of HEK293 cells.

Human embryonic kidney 293 (HEK293) cells have been successfully adapted from adherent to suspension culture and widely applied in both scientific research and the pharmaceutical industry. Although some studies investigated the variances between established adherent and suspension HEK293 cells of different strains, specific alterations in the cells during this consecutive process of suspension adaptation and possible factors driving this process have not been well described. Here, we adapted adherent HEK293 to suspension with desirable cell growth and high productivity for recombinant adenoviral vectors, and cells at several stages throughout the process were characterized. Slower cell growth, lower glucose uptake, increased lactate production, and weaker cell-surface adhesion were observed in suspension cells compared to their adherent counterparts. We further performed transcriptomics, proteomics, and metabolomics analysis to identify key cellular switches. A total of 2476 differentially expressed genes were found, including 1218 upregulated and 1258 downregulated genes in suspension cells. A similar and correlated pattern was observed in the proteomic study, and 702 differentially expressed metabolites were identified by untargeted metabolomics. In light of enrichment analysis, we summarized that HEK293 adherent cells survived and adapted to suspension culture via structural remodeling, metabolic shift and stress resistance. Our results provide a molecular enlightenment for suspension adaptation and potential directions for rational modification of HEK293 cell lines for future use. KEY POINTS: • Suspension adaptation reduced adhesion and reshaped the HEK293 cytoskeleton. • Multi-omics revealed metabolic rewiring and enhanced stress resistance. • An optimized suspension line outperformed an internal HEK293 suspension reference.

Humans↗

PubMed2025

Alevin-fry-atac enables rapid and memory frugal mapping of single-cell ATAC-seq data using virtual colors for accurate genomic pseudoalignment.

SUMMARY: Ultrafast mapping of short reads via lightweight mapping techniques such as pseudoalignment has significantly accelerated transcriptomic and metagenomic analyses with minimal accuracy loss compared to alignment-based methods. However, applying pseudoalignment to large genomic references, like chromosomes, is challenging due to their size and repetitive sequences. We introduce a new and modified pseudoalignment scheme that partitions each reference into "virtual colors." These are essentially overlapping bins of fixed maximal extent on the reference sequences that are treated as distinct "colors" from the perspective of the pseudoalignment algorithm. We apply this modified pseudoalignment procedure to process and map single-cell ATAC-seq data in our new tool alevin-fry-atac. We compare alevin-fry-atac to both Chromap and Cell Ranger ATAC. Alevin-fry-atac is highly scalable and, when using 32 threads, is 2.8 times faster than Chromap (the second fastest approach) while using only 33% of the memory required by Chromap. The resulting peaks and clusters generated from alevin-fry-atac show high concordance with those obtained from both Chromap and the Cell Ranger ATAC pipeline, demonstrating that virtual color-enhanced pseudoalignment directly to the genome provides a fast, memory-frugal, and accurate alternative to existing approaches for single-cell ATAC-seq processing. The development of alevin-fry-atac brings single-cell ATAC-seq processing into a unified ecosystem with single-cell RNA-seq processing (via alevin-fry) to work toward providing a truly open alternative to many of the varied capabilities of CellRanger. AVAILABILITY AND IMPLEMENTATION: Alevin-fry-atac is written in Rust and C++17, and is freely-available under a BSD 3-clause license. It is integrated into piscem (https://github.com/COMBINE-lab/piscem) and alevin-fry (https://github.com/COMBINE-lab/alevin-fry), and is also supported directly as part of simpleaf (https://github.com/COMBINE-lab/simpleaf).

Single-Cell Analysis↗

PubMed2003

Single primer amplification (SPA) of cDNA for microarray expression analysis.

The potential of expression analysis using cDNA microarrays to address complex problems in a wide variety of biological contexts is now being realised. A limiting factor in such analyses is often the amount of RNA required, usually tens of micrograms. To address this problem researchers have turned to methods of improving detection sensitivity, either through increasing fluorescent signal output per mRNA molecule or increasing the amount of target available for labelling by use of an amplification procedure. We present a novel DNA-based method in which an oligonucleotide is incorporated into the 3' end of cDNA during second-strand cDNA synthesis. This sequence provides an annealing site for a single complementary heel primer that directs Taq DNA polymerase amplification of cDNA following multiple cycles of denaturation, annealing and extension. The utility of this technique for transcriptome-wide screening of relative expression levels was compared to two alternative methodologies for production of labelled cDNA target, namely incorporation of fluorescent nucleotides by reverse transcriptase or the Klenow fragment. Labelled targets from two distinct mouse tissues, adult liver and kidney, were compared by hybridisation to a set of cDNA microarrays containing 6500 mouse cDNA probes. Here we demonstrate, through a dilution series of cDNA derived from 10 micro g of total RNA, that it is possible to produce datasets comparable to those produced with unamplified targets with the equivalent of 30 ng of total RNA. The utility of this technique for microarray analysis in cases where sample is limited is discussed.

Animals↗

PubMed2026

Genomic characterization and phylogenetic placement of Matryoshka RNA virus 1 associated with Plasmodium vivax malaria in Africa.

Plasmodium vivax is a major cause of human malaria. It harbours Matryoshka RNA virus 1 (MaRNAV-1), a bi-segmented positive-sense RNA virus. MaRNAV-1 was first described in P. vivax and is now recognized as part of a wider group of Matryoshka viruses. These viruses also infect other haemosporidian parasites such as Leucocytozoon and Haemoproteus. The presence of MaRNAV-1 in African-origin human P. vivax, however, has not been clearly established. This study investigated whether MaRNAV-1 is present in public African-origin P. vivax transcriptomic datasets. Any viral sequences recovered were characterized using comparative genomic and phylogenetic analyses. A secondary in silico analysis targeted African-origin P. vivax RNA-seq runs from public repositories. Although the search covered Africa, only Ethiopian datasets could be confidently identified, retrieved and compiled at the time. After quality control and screening for MaRNAV-1 RNA-dependent RNA polymerase (RdRp) signals, three high-confidence runs were selected for further analysis. Reference-guided reconstruction, ORF prediction, blast-based validation and RdRp phylogenetic analysis were performed. MaRNAV-1 was identified in three Ethiopian P. vivax malaria transcriptomes. This was supported by strong segment-level mapping, near-complete coverage, high mean depth and minimal low-depth masking. The recovered genomes showed the expected bisegmented organization of MaRNAV-1. Segment I was highly conserved and encoded the canonical RdRp in all three consensus sequences. Segment II showed the conserved organization of two overlapping hypothetical ORFs in all three consensus sequences. Blast analyses confirmed close similarity to MaRNAV-1 reference sequences. Phylogenetic inference grouped the Ethiopian sequences within the broader P. vivax-associated MaRNAV-1 lineage, alongside other recognized MaRNAV lineages distinct from more divergent narna-like viruses. These findings provide genomic evidence for MaRNAV-1 in publicly available African-origin P. vivax transcriptomic datasets and add to the emerging evidence for the virus in the African malaria context.

MaRNAV↗

PubMed2026

Integrative pooled transcriptomic analysis reveals shared and distinct molecular signatures in adult T-cell leukemia/lymphoma and peripheral T-cell lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphomas (PTCLs) are aggressive neoplasms of mature T cells with poor prognosis and limited therapies. ATLL originates from HTLV-1 infection, while PTCL comprises heterogeneous subtypes without a defined etiologic factor. Comparative molecular profiling of these malignancies remains limited. We conducted an integrative pooled transcriptomic analysis of publicly available Gene Expression Omnibus (GEO) microarray datasets to compare ATLL, PTCL, and normal T-cell samples. Differential expression, functional enrichment, and protein-protein interaction (PPI) network analyses were performed using STRING, Cytoscape, and Gephi. Key hub genes and functional modules were further analyzed through KEGG and Enrichr databases. Comparative analyses revealed upregulation of extracellular matrix (ECM) components (COL1A1, COL3A1, FN1, SPARC, THBS1) and immune-regulatory molecules (CD163, CXCL12-CXCR4, complement subunits). Shared pathways included ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling. PTCL showed enrichment in coagulation and angiogenesis, while ATLL displayed distinct enrichment of cytoskeletal, chemokine, immune-regulatory, and signaling-associated pathways. PPI networks identified ECM and chemokine signaling as key hubs, with subtype-specific modules related to immune regulation, proliferation, and metabolism. This integrative approach uncovers common and distinct oncogenic programs in ATLL and PTCL, emphasizing ECM remodeling and immune modulation as shared hallmarks. Hub genes such as COL1A1, FN1, and CXCL12-CXCR4 may represent candidate molecular signatures that warrant validation in independent patient cohorts and functional studies before their clinical utility can be established.

Humans↗

PubMed2026

Extracellular vesicle miR-93-5p cargo regulates glomerular endothelial cell damage in Alport syndrome.

Modulation of miRNA expression in glomerular cells is associated with renal disease. Here, we investigated the role of miR-93-5p in mitigating glomerular damage in Alport syndrome and whether the disease-modifying activity of extracellular vesicles from human amniotic fluid stem cells (hAFSC-EVs) is mediated by their miR-93-5p cargo. We identified downregulation of miR-93-5p specifically in glomerular endothelial cells in Alport syndrome along disease progression. Silencing of miR-93-5p in hAFSC-EVs changed the transcriptomic and proteomic profile, regulating EV disease-modifying activity. Compared with naive hAFSC-EVs, silenced hAFSC-EVs did not rescue glomerular endothelial function in vitro and did not restore kidney function in vivo. We established that hAFSC-EVs regulate VEGFR1 and VEGFR2 signaling by miR-93-5p cargo transfer, highlighting that miR-93-5p can restore glomerular endothelial cell biology. Spatial transcriptomics analysis of hAFSC-EV-injected kidneys showed that these EVs can reverse pathways altered during disease progression by stimulating proregenerative processes, specifically in the glomerulus, by regulating miR-93-5p targets. Alteration of glomerular endothelial cell transcriptomics and miR-93-5p targets was also confirmed in biopsies of patients with Alport syndrome using spatial molecular imaging. We demonstrated the critical role of miR-93-5p in glomerular endothelial cells and the capability of hAFSC-EVs to regulate miR-93-5p and its targets in Alport syndrome.

Humans↗

PubMed2014

A better understanding of why murine models of trauma do not recapitulate the human syndrome.

OBJECTIVE: Genomic analyses from blood leukocytes have concluded that mouse injury poorly reflects human trauma at the leukocyte transcriptome. Concerns have focused on the modest severity of murine injury models, differences in murine compared with human age, dissimilar circulating leukocyte populations between species, and whether similar signaling pathways are involved. We sought to examine whether the transcriptomic response to severe trauma in mice could be explained by these extrinsic factors, by utilizing an increasing severity of murine trauma and shock in young and aged mice over time, and by examining the response in isolated neutrophil populations. DESIGN: Preclinical controlled in vivo laboratory study and retrospective cohort study. SETTING: Laboratory of Inflammation Biology and Surgical Science and multi-institution level 1 trauma centers. SUBJECTS: Six- to 10-week-old and 20- to 24-month-old C57BL/6 (B6) mice and two cohorts of 167 and 244 severely traumatized (Injury Severity Score > 15) adult (> 18 yr) patients. INTERVENTIONS: Mice underwent one of two severity polytrauma models of injury. Total blood leukocyte and neutrophil samples were collected. MEASUREMENTS AND MAIN RESULTS: Fold expression changes in leukocyte and neutrophil genome-wide expression analyses between healthy and injured mice (p < 0.001) were compared with human total and enriched blood leukocyte expression analyses of severe trauma patients at 0.5, 1, 4, 7, 14, and 28 days after injury (Glue Grant trauma-related database). We found that increasing the severity of the murine trauma model only modestly improved the correlation in the transcriptomic response with humans, whereas the age of the mice did not. In addition, the genome-wide response to blood neutrophils (rather than total WBC) was also not well correlated between humans and mice. However, the expression of many individual gene families was much more strongly correlated after injury in mice and humans. CONCLUSIONS: Although overall transcriptomic association remained weak even after adjusting for the severity of injury, age of the animals, timing, and individual leukocyte populations, there were individual signaling pathways and ontogenies that were strongly correlated between mice and humans. These genes are involved in early inflammation and innate/adaptive immunity.

Adult↗